Enzymes are protein molecules which serve to accelerate the chemical reactions of living cells (often by several orders of magnitude). Without enzymes, most biochemical reactions would be too slow to even carry out life processes. Enzymes display great specificity and are not permanently modified by their participation in reactions. Since they are not changed during the reactions, enzymes can be cost effectively used as catalysts for a desired chemical transformation.
Transaminases are a specific class of enzymes that catalyze the direct amination of ketones to chiral amines. Enantiomerically pure chiral amines are key intermediates in the synthesizing of a number of pharmaceutical compounds that possess a wide range of biological activities. Currently there is considerable effort underway to develop efficient catalytic methods for their preparation utilizing biocatalysts. Recently transaminases have emerged as promising biocatalysts for chiral amine production. Truppo et al., Efficient kinetic resolution of recemic amines using a transaminase in combination with an amino acid oxidase, Chem. Commun., 2009, 2127-2129; and Truppo et al., Efficient Production of Enantiomerically Pure Chiral Amines at Concentrations of 50 g/L Using Transaminases, Organic Process Research & Development 2010, 14, 234-237.
For example, rhodium-catalized asymmetric enamine hydrogenation was originally used for the large-scale manufacture of the antidiabetic compound sitagliptin. The rhodium was replaced with a tranaminase which ultimately has lead to an enzymatic process that reduces waste, improves yield and safety, and eliminates the need for a metal catalyst. Moreover, the resultant biocatalyst showed broad applicability toward the synthesis of chiral amines that previously were accessible only via resolution. Savile et al., Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture, Science, Vol. 329, pgs. 305-309, 16 Jul. 2010.
Though advances in producing chiral amines using transaminases have been highly regarded, there still exits some drawbacks to the enzymatic process. Currently enzymatic processes can only be run in aqueous solvent systems as the transaminases are not stable in 100% organic solvents. Additionally, during product amine isolation, the transaminase catalyst is deactivated and discarded resulting in the inability to reuse the catalyst.
Thus, though attempts have been made to immobilize transaminases none have been successful in overcoming their lack of stability, more specifically their lack of stability in organic solvents.